Thesis (M.Sc)-Cairo University, 2025.

Bibliography: pages135–137.

Based on the principles of green and white analytical chemistry, new
univariate and chemometric-aided UV spectrophotometric techniques were
created for the simultaneous determination of olanzapine (OLA), fluoxetine HCl
(FLU), and its toxic impurity 4-(Trifluoromethyl) phenol (FMP), without the
need for earlier separation. Through dual-wavelength ratio spectrum analysis,
OLA (4-20 ȝg/mL) and FLU (5-50 ȝg/mL) were successfully determined in the
presence of FMP with satisfactory performance characteristics, including 98-
102% accuracy and precision (RSD <2%). the method was complied with ICH
standards. Chemometric techniques, including partial least squares (PLS) and
artificial neural networks (ANNs), demonstrated superior performance with Latin
hypercube sampling (LHS) for systematically generate representative validation
sets, overcoming the limitations of conventional random data. The analytical
methods were validated across concentration ranges of 2-20 ȝg/mL for both OLA
and FMP, and 5-50 ȝg/mL for FLU. The PLS model demonstrated root mean
square errors of prediction (RMSEP) of 0.087, 0.048, and 0.159 for OLA, FMP,
and FLU respectively. Superior performance was observed with ANN, showing
lower RMSEP values (0.056, 0.047, and 0.087), respectively. Environmental
impact was evaluated using multiple assessment tools including NEMI, ESA,
Complex GAPI, AGREE, and RGB 12 metrics., demonstrating strong
environmental compliance. Statistical analysis revealed no significant
differences (P > 0.05) compared to existing methods. The methods were
successfully applied to pure powders and pharmaceutical capsules.
A novel, eco-friendly high performance liquid chromatography (HPLC)
method was developed for the simultaneous determination of pregabalin (PRE),
milnacipran hydrochloride (MIL), and duloxetine hydrochloride (DLU), FDA-
approved fibromyalgia drugs. This method addresses challenges posed by their
structural diversity and PRE's poor UV absorbance. With the aim of reducing run
time and eliminating derivatization, it avoids hazardous reagents and reduces
waste. Separation was achieved on a C18 column using a mobile phase of 45%
0.03M sodium dihydrogen phosphate buffer (pH 3.5), 30% acetonitrile, and 25%
methanol at flow rate 0.9 ml/min, with UV detection at 210 nm. The method
showed extended linearity (100–1600 μg/ml for PRE, 2–40 μg/ml for MIL and
DLU) and quantification limits of 91.2, 1.326, and 1.872 μg/ml, respectively.
Validated per ICH guidelines and applied to pure drugs and formulations, its
sustainability was confirmed by AGREE and Complex GAPI greenness
assessments.
An innovative chemometrics-assisted UV spectrophotometric methods
for simultaneous quantification of cinnarizine (CIN), domperidone (DOM), and
benzophenone (BNZ), a carcinogenic CIN degradation product, achieved without
the need for prior separation. Predictive models using Classical Least Squares
(CLS), PLS, and Multivariate Curve Resolution–Alternating Least Squares
(MCR-ALS) were developed, with a strategically optimized validation set of 13
mixtures generated via MATLAB’s Candexch algorithm (D-optimal design).
The methods exhibited robust linearity across 4–20 μg/mL (CIN), 3–15 μg/mL
(DOM), and 1–5 μg/mL (BNZ). Calibration performance was excellent, with root
mean square errors of calibration (RMSEC) values of 0.036–0.062 (CLS), 0.013–
0.024 (PLS), and 0.009–0.012 (MCR-ALS), with MCR-ALS demonstrating the
highest accuracy and stability. Validation confirmed recovery rates of 98–102%,
while RMSEP values for the validation set ranged from 0.042–0.201 (CLS),
0.035–0.187 (PLS), and 0.022–0.154 (MCR-ALS), with MCR-ALS consistently
outperforming other methods in predictive accuracy. Environmental
sustainability was extensively assessed using NEMI, Complex GAPI, AGREE,
BAGI, RGB12, Spider Chart, Carbon Footprint Analysis, GSST, and the NQS
Index, confirming exceptional eco-friendliness and alignment with (UN-SDGs).
A novel environmentally friendly analytical method utilizing Fourier
Transform Infrared (FTIR) spectroscopy was developed for the simultaneous
quantification of CIN and DOM without the need for prior separation. The
approach is based on analyzing the first derivative spectra within the infrared
range of 4600–FPၱï&,1LVTXDQWLILHGDWFPၱïZKHUH'20]HUR
FURVVLQJDQG'20LVGHWHUPLQHGDWFPၱïZKHUH&,1VKRZV]HURFURVVLQJ
The method exhibited excellent linearity within the concentration ranges of 0.6-
3.3 μg/mg for CIN and 0.4–2.4 μg/mg for DOM. Additionally, the limits of
detection (LOD) for both drugs were determined to be 0.171 and 0.128 μg/mg
for CIN and DOM respectively, confirming the method’s sensitivity. The
developed method was validated according to ICH guidelines and successfully
applied to both pure substances and pharmaceutical formulations.

تقدم هذه الرسالة استراتيجية تحليلية شاملة لتحديد كميات الخلطات الصيدلانية المعقدة المستخدمة في علاج اضطرابات الجهاز العصبي المركزي (CNS).تدمج هذه الاستراتيجية تقنيات التحليل الطيفي المتقدمة، وبشكل خاص التحليل الطيفي بالأشعة فوق البنفسجية (UV) والتحليل الطيفي بالأشعة تحت الحمراء باستخدام تحويل فورييه (FTIR) ، مع طرق الكروماتوغرافيا مثل الكروماتوغرافيا السائلة عالية الأداء (HPLC) .تستخدم الدراسة طرق احادية مثل طيف النسبة ذو الطول الموجي المزدوج ، وتحليل الطيف المشتق، بالإضافة إلى عدد من أدوات الكيمياء الحسابية (الكيمومتريكس) ، بما في ذلك المربعات الصغرى الكلاسيكية (CLS) ، والمربعات الصغرى الجزئية (PLS) ، والشبكات العصبية الاصطناعية (ANNs) ، وحل المنحنيات المتعددة المتغيرات - المربعات الصغرى المتناوبة (MCR-ALS)، لتعزيز تفسير البيانات وأداء الطريقة.تم إجراء تصميم التجارب والتحقق من النموذج باستخدام أخذ العينات من الهيبركيوب اللاتيني (LHS) وتصميم D- optimal المنفذ عبر خوارزميةcandexchفي MATLAB. وقد ضمنت هذه الطريقة متانة الطريقة، والدقة، والكفاءة التشغيلية مع الحفاظ على الاستدامة البيئية.أظهرت المنهجيات المطورة دقة عالية، وموثوقية، وكفاءة بيئية، مما يجعلها مناسبة لمراقبة الجودة الصيدلانية الحديثة. تم إجراء تقييمات للون الأخضر، واللون الأبيض، واللون الأزرق، إلى جانب اختيار المذيبات الموجه بواسطة أداة اختيار المذيبات الخضراء (GSST) ومخطط العنكبوت لتقييم مؤشر الخضرة. (SDAGI) أكدت التقييمات باستخدام مؤشر الطرق البيئية الوطنية (NEMI)، ومقياس البيئة التحليلية (ESA)، ومؤشر الإجراءات التحليلية الخضراء التكميليالمعقد (Complex GAPI)، ومقياس الخضرة التحليلية (AGREE)، وتحليل البصمة الكربونية، ومؤشر قابلية الاستخدام الأزرق (BAGI) ، ونموذج الأحمر والأخضر والأزرق 12 (RGB12)، ومؤشر الحاجةو الجودة والاستدامة (NQS)على الالتزام القوي بمبادئ الكيمياء التحليلية الخضراء (GAC) والكيمياء التحليلية البيضاء (WAC). ومواءمته مع أهداف التنمية المستدامة للأمم المتحدة.(UN-SDGs)

Issues also as CD.

Text in English and abstract in Arabic & English.